{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:41:18Z","timestamp":1778690478681,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2006,10,26]],"date-time":"2006-10-26T00:00:00Z","timestamp":1161820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p><jats:bold>Background: <\/jats:bold> Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol\u2010induced degeneration is unknown, but is not simple glutamate\u2013<jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (NMDA) excitotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol\u2010induced brain damage, we administered 4 antioxidants, e.g., butylated hydroxytoluene (BHT), ebselen (Eb), vitamin E (VE), and blueberry (BB) extract, during binge ethanol treatment and assessed various measures of neurodegeneration.<\/jats:p><jats:p><jats:bold>Methods: <\/jats:bold> Adult Sprague\u2013Dawley rats were treated with intragastric ethanol 3 times per day (8\u201312 g\/kg\/d) alone or in combination with antioxidants or isocaloric diet for 4 days. Animals were killed, and brains were perfused and extracted for histochemical silver stain determination of brain damage, markers of neurogenesis, or other immunohistochemistry. Some animals were used for determination of nuclear factor <jats:italic>\u03ba<\/jats:italic> B (NF\u2010<jats:italic>\u03ba<\/jats:italic>B)\u2013DNA binding by electrophoretic mobility shift assay (EMSA) or for reverse transcription\u2013polymerase chain reaction (RT\u2010PCR) of cyclooxygenase 2 (COX2).<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> Binge ethanol induced corticolimbic brain damage and reduced neurogenesis. Treatment with BHT reversed binge induced brain damage and blocked ethanol inhibition of neurogenesis in all regions studied. Interestingly, the other antioxidants studied, e.g., Eb, VE, and BB, did not protect against binge\u2010induced brain damage. Binge ethanol treatment also caused microglia activation, increased NF\u2010<jats:italic>\u03ba<\/jats:italic>B\u2013DNA binding and COX2 expression. Butylated hydroxytoluene reduced binge\u2010induced NF\u2010<jats:italic>\u03ba<\/jats:italic>B\u2013DNA binding and COX2 expression.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> Binge\u2010induced brain damage and activation of NF\u2010<jats:italic>\u03ba<\/jats:italic>B\u2013DNA binding are blocked by BHT. These studies support a neuroinflammatory mechanism of binge ethanol\u2010induced brain damage.<\/jats:p>","DOI":"10.1111\/j.1530-0277.2006.00239.x","type":"journal-article","created":{"date-parts":[[2006,10,26]],"date-time":"2006-10-26T08:45:01Z","timestamp":1161852301000},"page":"1938-1949","source":"Crossref","is-referenced-by-count":160,"title":["BHT Blocks NF\u2010<i>\u03ba<\/i>B activation and Ethanol\u2010Induced Brain 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